5-59214500-G-T

Position:

• chr5-59214500-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001364601.1(PDE4D):​c.*1273C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,094 control chromosomes in the GnomAD database, including 1,145 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1145 hom., cov: 32)
• Consequence: PDE4D NM_001364601.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220

Genes affected

PDE4D (HGNC:8783): (phosphodiesterase 4D) This gene encodes one of four mammalian counterparts to the fruit fly 'dunce' gene. The encoded protein has 3',5'-cyclic-AMP phosphodiesterase activity and degrades cAMP, which acts as a signal transduction molecule in multiple cell types. This gene uses different promoters to generate multiple alternatively spliced transcript variants that encode functional proteins.[provided by RefSeq, Sep 2009]

PDE4D (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4D	NM_001104631.2	c.647+1277C>A		intron_variant		ENST00000340635.11	NP_001098101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000340635.11	c.647+1277C>A		intron_variant		1	NM_001104631.2	ENSP00000345502.6

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16866 AN: 151976 Hom.: 1144 Cov.: 32

Gnomad AFR AF: 0.0412

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.0809

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.106

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.111 AC: 16868 AN: 152094 Hom.: 1145 Cov.: 32 AF XY: 0.113 AC XY: 8374 AN XY: 74338

Gnomad4 AFR AF: 0.0413

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0878

Gnomad4 EAS AF: 0.0809

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.105

Alfa AF: 0.129 Hom.: 2565

Bravo AF: 0.0981

Asia WGS AF: 0.123 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs425384; hg19: chr5-58510326;